Age-related Changes in the Kinetics of Water Transport in Normal Human Lenses

Moffat, Bradford A.; Landman, Kerry A.; Truscott, Roger J.W.; Sweeney, Matthew; Pope, J. H.

doi:10.1006/exer.1999.0747

Cited by 102 publications

(87 citation statements)

References 14 publications

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“…These in situ observations corroborate the observations on isolated human lenses [64,65] and support the existence of a diffusion barrier in the lens outer cortex. In contrast, however, to the results by Moffat et al [64,65], who found nearly identical diffusion rates in the anterior and posterior poles of isolated human lenses, we observed lower signals in the posterior lens pole.…”

Section: Paracellular Transportsupporting

confidence: 89%

“…This means that for the integrity and transparency of the deep cortex and nucleus, the limited diffusion might not be a serious problem. MRI studies on isolated human lenses [64,65] and preliminary in situ observations in bovine lenses (electronic supplementary material, figure S1) support a restricted entry of water and ions into the deep cortex and nucleus of the lens. Two recent studies [104,105] have shown that early age-related opacities and cortical cataracts have their origin in and stay restricted to the lens cortex, while the lens nucleus remains unaffected, supporting the independence of the lens nucleus behind the barrier compared with the more peripheral regions beyond the barrier.…”

Section: Summary and Discussionmentioning

confidence: 74%

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Homeostasis in the vertebrate lens: mechanisms of solute exchange

Dahm

Marle

Quinlan

et al. 2011

Phil. Trans. R. Soc. B

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The eye lens is avascular, deriving nutrients from the aqueous and vitreous humours. It is, however, unclear which mechanisms mediate the transfer of solutes between these humours and the lens' fibre cells (FCs). In this review, we integrate the published data with the previously unpublished ultrastructural, dye loading and magnetic resonance imaging results. The picture emerging is that solute transfer between the humours and the fibre mass is determined by four processes: (i) paracellular transport of ions, water and small molecules along the intercellular spaces between epithelial and FCs, driven by Na þ -leak conductance; (ii) membrane transport of such solutes from the intercellular spaces into the fibre cytoplasm by specific carriers and transporters; (iii) gap-junctional coupling mediating solute flux between superficial and deeper fibres, Na þ /K þ -ATPase-driven efflux of waste products in the equator, and electrical coupling of fibres; and (iv) transcellular transfer via caveoli and coated vesicles for the uptake of macromolecules and cholesterol. There is evidence that the Na þ -driven influx of solutes occurs via paracellular and membrane transport and the Na þ /K þ -ATPase-driven efflux of waste products via gap junctions. This micro-circulation is likely restricted to the superficial cortex and nearly absent beyond the zone of organelle loss, forming a solute exchange barrier in the lens.

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Section: Paracellular Transportsupporting

confidence: 89%

Section: Summary and Discussionmentioning

confidence: 74%

Homeostasis in the vertebrate lens: mechanisms of solute exchange

Dahm

Marle

Quinlan

et al. 2011

Phil. Trans. R. Soc. B

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“…In particular, a pronounced "ring" of high DHSM concentration was observed in lenses older than 60 years, and its geometric dimensions correspond in size to that of the barrier to diffusion ( 5,6 ). The elevated concentrations of sphingomyelins in this zone were confi rmed using quantitative methods based on electrospray ionization mass spectrometry.…”

Section: Discussionmentioning

confidence: 94%

Sphingolipid distribution changes with age in the human lens

Deeley

Hankin

Friedrich

et al. 2010

Journal of Lipid Research

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characterizing these can have clinical relevance for understanding the molecular basis of ocular conditions such as presbyopia ( 2 ) and nuclear cataract ( 3, 4 ).It is not known which are the critical factors predisposing the human lens to age-related nuclear (ARN) cataract. Research from one of us, over many years, suggests that the formation of an internal barrier to the diffusion of small molecules may be a key event in the onset of this pathology ( 5, 6 ). The barrier forms in the normal lens at middle age and uncouples the center of the lens from the metabolically active outer region. Because the lens grows continuously throughout life, the outmost part of the lens is the region that was formed most recently and has the highest concentration of active enzymes ( 7,8 ). It is where the major antioxidant glutathione (GSH) is synthesized and the oxidized form of glutathione rereduced ( 9, 10 ). Since GSH is essential for maintaining a reducing environment in the lens center and for protection of protein structure, formation of the barrier allows oxidative modifi cation of nuclear proteins that is the hallmark of nuclear cataract. The dimensions of the barrier region (7 mm equatorial × 3 mm axial) corresponds to the part of the adult lens that was synthesized immediately after birth ( 11,12 ).Recent data implicate the binding of denatured proteins to the fi ber cell membrane as the mechanism responsible for the barrier ( 13 ), possibly by occluding the membrane pores that normally facilitate the movement of GSH and water from cell to cell via connexon ( 14 ) and aquaporin 0 ( 15 ) channels, respectively. Moreover, aquaporin 0 requires interaction with distinct membrane lipids to form its correct functional conformation ( 15 ). If interactions with fi ber cell Abstract The formation of an internal barrier to the diffusion of small molecules in the lens during middle age is hypothesized to be a key event in the development of age-related nuclear (ARN) cataract. Changes in membrane lipids with age may be responsible. In this study, we investigated the effect of age on the distribution of sphingomyelins, the most abundant lens phospholipids. Human lens Due to a lack of turnover ( 1 ), the lens is an ideal tissue for examining age-related changes to biomolecules, and

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“…Aging of the human lens is associated with presbyopia (Glasser and Campbell 1998;Glasser et al 2001;) and cataract (Harding 2002;Truscott 2005). In the case of age-related nuclear cataract, it has been proposed that the development of a barrier to diffusion of metabolites between the lens cortex and nucleus at middle age may be a prerequisite (Sweeney and Truscott 1998;Moffat et al 1999). Recent data suggest that the reason for the onset of the barrier is due to the binding of crystallins to fiber cell membranes (Friedrich and Truscott 2009) and in this way the membrane pores are occluded.…”

Section: Discussionmentioning

confidence: 99%

Instability of the cellular lipidome with age

Hughes

Deeley

Blanksby

et al. 2011

AGE

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The human lens nucleus is formed in utero, and from birth onwards, there appears to be no significant turnover of intracellular proteins or membrane components. Since, in adults, this region also lacks active enzymes, it offers the opportunity to examine the intrinsic stability of macromolecules under physiological conditions. Fifty seven human lenses, ranging in age from 12 to 82 years, were dissected into nucleus and cortex, and the nuclear lipids analyzed by electrospray ionization tandem mass spectrometry. In the first four decades of life, glycerophospholipids (with the exception of lysophosphatidylethanolamines) declined rapidly, such that by age 40, their content became negligible. In contrast the level of ceramides and dihydroceramides, which were undetectable prior to age 30, increased approximately 100-fold. The concentration of sphingomyelins and dihydrosphingomyelins remained unchanged over the whole life span. As a consequence of this marked alteration in composition, the properties of fiber cell membranes in the centre of young lenses are likely to be very different from those in older lenses. Interestingly, the identification of age 40 years as a time of transition in the lipid composition of the nucleus coincides with previously reported macroscopic changes in lens properties (e.g., a massive age-related increase in lens stiffness) and related pathologies such as presbyopia. The underlying reasons for the dramatic change in the lipid profile of the human lens with age are not known, but are most likely linked to the stability of some membrane lipids in a physiological environment.

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Age-related Changes in the Kinetics of Water Transport in Normal Human Lenses

Cited by 102 publications

References 14 publications

Homeostasis in the vertebrate lens: mechanisms of solute exchange

Homeostasis in the vertebrate lens: mechanisms of solute exchange

Sphingolipid distribution changes with age in the human lens

Instability of the cellular lipidome with age

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